Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Research progress of anti-drug resistance in traditional Chinese medicine / 中国中药杂志

Bacterial drug resistance has been always the focus of the world. With the abuse of antibiotics and the emerging of "Superbug" in the world, the harm of drug resistance to human beings is more and more serious, with an uncontrollable trend. Today, with the relative lack of antibiotics, people pay more attention to Chinese herbal medicines with a wide range of sources, high security, less toxic side effects and mysterious anti-drug resistance mechanism, hoping to find new ways or new ideas to solve the problem of drug resistance. In recent years, the screening, extracting and isolating of effective drug resistance inhibitors from natural plants and traditional Chinese Medicine, as well as the investigation in mechanism of anti-drug resistance, have become a hot research in the field of medicine. In this paper, we would analyze and summarize the action mechanism of bacterial drug resistance, characteristics and advantages of anti-drug resistance of traditional Chinese medicine, as well as the herbal ingredients with anti-drug resistance effect, hoping to provide certain theoretical basis and research ideas for solving the problem of bacterial drug resistance and developing new green Chinese antibiotics.

Effects of gonadotropin releasing hormone analog and growth hormone on height in girls with idiopathic central precocious puberty / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP).</p><p><b>METHODS</b>Eighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 ±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03 ±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups.</p><p><b>RESULTS</b>HtSDS-BA was significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values in near adult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant.</p><p><b>CONCLUSIONS</b>Both GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.</p>

Impact of neonatal exposure to different doses of bisphenol A on puberty in female rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of neonatal exposure to different doses of bisphenol A (BPA) on the vaginal opening day (VOD), hypothalamic Kiss-1 mRNA expression, and ovarian estrogen receptor (ER) mRNA expression in female rats.</p><p><b>METHODS</b>Neonatal female Sprague-Dawley (SD) rats were randomly divided into six groups: blank control, vehicle, 17β-estradiol (17β-estradiol, E2, 10 μg/d), low-dose BPA [25 μg(kg·d)], medium-dose BPA [50 μg(kg·d)], and high-dose BPA groups [250 μg(kg·d)]. The rats were subcutaneously injected with respective agents on postnatal days 0-6. The VOD was recorded, and each rat was sacrificed on the same day. The hypothalamus and ovary were taken and weighed, and the organ coefficients of hypothalamus and ovary were calculated. The hypothalamic Kiss-1 mRNA expression and ovarian ERα and ERβ mRNA expression were measured by real-time PCR.</p><p><b>RESULTS</b>Compared with the control group, the E2 and medium- and high-dose BPA groups had advanced VOD, and the E2 group had significantly reduced hypothalamic Kiss-1 mRNA expression and ovarian ERβ mRNA expression (P<0.05).</p><p><b>CONCLUSIONS</b>Neonatal exposure to medium- and high-dose BPA[50 and 250 μg/(kg·d)] can induce precocious puberty in rats, but it may not result from the change in hypothalamic Kiss-1 mRNA expression. Neonatal exposure to low-dose BPA [25 μg/(kg·d)] does not induce precocious puberty in rats.</p>

Relationship between methimazole and antineutrophil cytoplasmic antibody-positive vasculitis / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between methimazole (MMI) and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis.</p><p><b>METHODS</b>Thirty-three cases with Graves' disease were tested for serum ANCA before and after taking MMI. At the same time, clinicopathological data of two patients with Graves' disease who had antineutrophil cytoplasmic antibody-positive vasculitis during treatment with MMI were analyzed.</p><p><b>RESULTS</b>Two patients developed antineutrophil cytoplasmic antibody-positive vasculitis during the medication with MMI for 5-6 years; their major clinical manifestations were hematuria and renal failure. Renal biology showed renal vasculitis and vascular necrosis. The disease was relieved after treatment with immunosuppressor. Serum ANCA in the 33 cases was negative before taking MMI. In 3 cases serum ANCA became positive after taking MMI for 2 months, 3 months and 2 years, respectively. The positive rate is 9% (3/33). The major finding was microscopic hematuria. ANCA positive rate was significantly higher after taking MMI than that before taking MMI (chi2) = 5.3, P < 0.05). Microscopic hematuria disappeared after general treatment.</p><p><b>CONCLUSION</b>There may be a relationship between methimazole and development of antineutrophil cytoplasmic antibody-positive vasculitis. Renal impairment can occur. The signs and symptoms of the vasculitis can disappear after proper treatment.</p>